Objective:To observe the electrocardiogram (ECG) changes of programmed death receptor 1 (PD-1)/programmed death receptor-ligand 1 (PD-L1) immune checkpoint inhibitors before and after immunotherapy of patients during clinical antitumor process, and to explore the occurrence and influencing factors of cardiotoxicity of immune checkpoint inhibitors.Methods:A total of 93 patients with locally advanced or metastatic solid tumors confirmed by pathological diagnosis in Cancer Hospital of Chinese Academy of Medical Sciences from October 1, 2019 to September 30, 2020 were selected and treated with PD-1/PD-L1 inhibitor monotherapy. Groups were divided according to immunotherapy regimen: Group A (drug code: 609A), 16 patients were given 1 mg/kg of the drug for 21 days; Group B (drug code: HX008), 23 patients were treated with 200mg for 21 days; Group C (drug code: GB226), 28 patients were treated with 3mg/kg for 14 days; Group D (drug code: LP002), 26 patients were treated with 900mg for 14 days. The patients were monitored and followed up for 10 cycles. The ECG results of each group were recorded, and the correlation between ECG abnormality and cardiotoxicity was analyzed.Results:A total of 75 patients showed abnormal ECG that met the diagnostic criteria. There was no significant difference in abnormal ECG rate after immunotherapy in group A ( P＞0.05), while the incidence of adverse cardiac events increased after immunotherapy in group B ( P＜0.05), and the abnormal ECG rate increased significantly after chemotherapy in group C and group D. There was statistical difference before and after immunotherapy ( P＜0.001). The number of abnormal cases in group A (8 cases, 50.0%, 8/16) was significantly lower than that of group B (20 cases, 87.0%, 20/23). The number of abnormal cases in group C and group D was 24 (85.7%) and 23 (88.4%), respectively, without statistical difference ( P＞0.05), but their abnormal rates of ECG were higher than that in group A. The incidence of electrical adverse events in immunotherapy center of patients with underlying diseases was 1.93 times higher than that of patients without underlying diseases. The incidence of central electrical adverse events during immunotherapy in group B, C and D was 6.667, 6.000 and 7.667 times higher than that in group A, respectively. Conclusions:The high sensitivity of early ECG changes induced by immune checkpoint inhibitors enables early prediction of related cardiotoxicity. The presence or absence of comorbid underlying disease and drug dosage are correlated with the occurrence of adverse cardiac events, and these early changes provide a evidence for clinical treatment and prevention.

Objective:To observe the electrocardiogram (ECG) changes of programmed death receptor 1 (PD-1)/programmed death receptor-ligand 1 (PD-L1) immune checkpoint inhibitors before and after immunotherapy of patients during clinical antitumor process, and to explore the occurrence and influencing factors of cardiotoxicity of immune checkpoint inhibitors.Methods:A total of 93 patients with locally advanced or metastatic solid tumors confirmed by pathological diagnosis in Cancer Hospital of Chinese Academy of Medical Sciences from October 1, 2019 to September 30, 2020 were selected and treated with PD-1/PD-L1 inhibitor monotherapy. Groups were divided according to immunotherapy regimen: Group A (drug code: 609A), 16 patients were given 1 mg/kg of the drug for 21 days; Group B (drug code: HX008), 23 patients were treated with 200mg for 21 days; Group C (drug code: GB226), 28 patients were treated with 3mg/kg for 14 days; Group D (drug code: LP002), 26 patients were treated with 900mg for 14 days. The patients were monitored and followed up for 10 cycles. The ECG results of each group were recorded, and the correlation between ECG abnormality and cardiotoxicity was analyzed.Results:A total of 75 patients showed abnormal ECG that met the diagnostic criteria. There was no significant difference in abnormal ECG rate after immunotherapy in group A ( P＞0.05), while the incidence of adverse cardiac events increased after immunotherapy in group B ( P＜0.05), and the abnormal ECG rate increased significantly after chemotherapy in group C and group D. There was statistical difference before and after immunotherapy ( P＜0.001). The number of abnormal cases in group A (8 cases, 50.0%, 8/16) was significantly lower than that of group B (20 cases, 87.0%, 20/23). The number of abnormal cases in group C and group D was 24 (85.7%) and 23 (88.4%), respectively, without statistical difference ( P＞0.05), but their abnormal rates of ECG were higher than that in group A. The incidence of electrical adverse events in immunotherapy center of patients with underlying diseases was 1.93 times higher than that of patients without underlying diseases. The incidence of central electrical adverse events during immunotherapy in group B, C and D was 6.667, 6.000 and 7.667 times higher than that in group A, respectively. Conclusions:The high sensitivity of early ECG changes induced by immune checkpoint inhibitors enables early prediction of related cardiotoxicity. The presence or absence of comorbid underlying disease and drug dosage are correlated with the occurrence of adverse cardiac events, and these early changes provide a evidence for clinical treatment and prevention.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Background::Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated.Methods::We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (each from three CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9. Results::Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A, AQP5, and MUC5AC. CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment. Conclusions::Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.

Humans ; Coronary Artery Disease/surgery* ; Percutaneous Coronary Intervention ; Heart ; Treatment Outcome ; Coronary Angiography

Objective: To understand reason for the difference of supplementary immunization activities (SIA) using measles-containing vacline (MV) among different types of universities in China. Methods: Ten universities from one city were selected by using purposive sampling method. Qualitative interviews were conducted on the implementation of MV SIA in universities, and the differences of measles vaccination and the reasons were analyzed. Results: The MV vaccination rates in the 10 universities in 2017 were 54%, 96%,95%,97%,81%,93%,13%,12%,10% and 21% respectively.The rate of four-year universities was higher than that of three-year colleges; and the rate of public universities was higher than that of private schools; the rate of provincial universities was higher than that of central government administered universities; the vaccination rates also vary within central government administered universities.The level, ownership and affiliation of colleges and universities led to the differences in medical qualification, administrators’ risk perception of disease and vaccines, and the relationship between the schools and local CDC, which in turn affected the implementation of vaccination in universities. Conclusion The different attributes of universities are the fundamental reasons that lead to the differences in the rate of MV SIA in Chinese universities. It is suggested that the differences of university attributes should be considered in the process of implementation of the policy of immunization in universities.And the vaccination policy in universities should be strengthened, the risk communication of universities, especially private universities, should be improved, and the working relationship of the Ministry of Health and the Ministry of Education should be enhanced.

Objective To investigate the antimicrobial resistance proifle in the clinical bacterial strains isolated from Peking Union Medical College Hospital during 2014.Methods A total of 8 295 nonduplicate clinical isolates were collected. Disc diffusion test (Kirby-Bauer method) and automated systems were employed to study the antimicrobial susceptibility. The data were analyzed by using WHONET 5.6 software according to CLSI 2014 breakpoints.Results Of the 8 295 isolates, 67.4% were gram-negative, and 32.6% were gram-positive. The top 10 most frequently isolated bacteria were:E. coli(18.1%),P. aeruginosa (10.8%),K. pneumoniae (10.2%),S. aureus (9.8%),
A. baumannii(9.2%),E. faecalis (6.3%),E. faecium (4.1%), coagulase-negativeStaphylococcus (4.1%),E. cloacae (3.1%) andS. maltophilia (2.9%). Methicillin resistant strains inS. aureus (MRSA) and coagulase negativeStaphylococcus (MRCNS) accounted for average of 28.4% and 66.5%, respectively. The resistance rates of MR strains to β-lactams and other antimicrobial agents were much higher than those MS strains. Overall, 81.3% of MRSA strains were still susceptible to trimethoprim-sulfamethoxazole, while 81.1% of MRCNS strains were susceptible to rifampin. No staphylococcal strains were resistant to vancomycin, teicoplanin or linezolid. The resistance rate ofE. faecalis strains to most of the drugs tested (except chloramphenicol) was much lower than those ofE. faecium. Several strains of bothE. faecium andE. faecalis were found resistant to vancomycin and teicoplanin, which were Van-A and Van-B types based on their phenotype. No linezolid resistant enterococcal strains were found. Data showed that 90.8% ofβ-hemolyticStreptococcus strains were susceptible to penicillin. ESBLs-producing strains accounted for 54.2%, 31.0% and 28.9% inE. coli,Klebsiella spp (K. pneumoniae andK. oxytoca) andP. mirabilis, respectively.Enterobacteriaceae isolates were still highly susceptible to carbapenems. Overall, no more than 3.3% of these strains were resistant to carbapenems. A few extensively drug-resistant strains ofK. pneumoniae (1.3%, 11/842) were identiifed. The resistance rates ofP. aeruginosa to imipenem and meropenem were 17.5% and 11.8%, respectively.P. aeruginosa isolates showed the lowest resistance rate (5.9%) to amikacin. And 69.0% and 67.4% ofA. baumanniiisolates were resistant to imipenem and meropenem.A. baumannii isolates showed the lowest resistance rates to cefoperazone-sulbactam and minocycline (47.8% and 28.7%), respectively. The prevalence of extensively drug-resistant strains was 32.3% inA. baumannii and 1.8% inP. aeruginosa. The prevalence of β-lactamase inH. inlfuenzae was 33.7%. More than 93.0% ofS. pneumoniae strains were resistant to erythromycin and clindamycin.Conelusions Bacterial resistance is still increasing in this hospital, especially carbapenem resistantEnterobacteriaceae. It is necessary to take effective hospital infection control measures and use antibiotics rationally.

OBJECTIVE:To establish a method for the content determination of eudesmin in Zanthoxylum simulans. METH-ODS:HPLC was performed on the column of Kromasil C18 with mobile phase of acetonitrile-water(56:44,V/V)at flow rate of 1.0 ml/L,detection wavelength was 221 nm,column temperature was 25 ℃. RESULTS:The linear of eudesmin was 0.208-2.08 μg (r=0.999 8);RSDs of precision,reproducibility and stability tests were lower than 2.0%;recovery was 96.18%-103.04%(RSD=2.58,n=6). CONCLUSIONS:The method is simple and good reproducibility,and can be used for the content determination of eu-desmin in Z. simulans.

Objective To investigate the profile of antimicrobial resistance in clinical isolates from the patients in Peking Union Medical College Hospital during 2012.Methods A total of 6 662 nonduplicate clinical isolates were collected.Disc diffusion test or Kirby-Bauer method and automated systems were employed to study the antimicrobial resistance.The data were analyzed by WHONET 5.6 software according to CLSI 2012 breakpoints.Results Of the 6 662 bacterial strains included in this analysis, gram negative organisms and gram positive cocci accounted for 66.7% (4 446/6 662)and 33.3% (2 216/6 662),respectively. The top 10 most frequently isolated microorganisms were E.coli (17%),P .aeruginosa (11.4%),A.baumannii (11.4%), S.aureus (11.2%),K.pneumoniae (9.2%),E.faecalis (8.4%),E.faecium (4.1%),coagulase negative Staphylococcus (3.3%),E.cloacae (3.1%)and S.maltophilia (3.1%).About 39.9% of the S.aureus strains and 73.4% of the coagulase negative Staphylococcus were methicillin-resistant.No staphylococcal strains were found resistant to vancomycin,teicoplanin or linezolid.A few of vancomycin-or teicoplanin-resistant strains were identified in both E.faecium and E.faecalis.No lin-ezolid resistant strains were found.ESBLs-producing strains accounted for 53.0%,25.7% and 27.0% in E.coli,Klebsiella spp.(K.pneumoniae and K.oxytoca)and P .mirabilis, respectively.The Enterobacteriaceae strains were still highly susceptible to carbapenems. Overall, less than 2.6% of these strains were resistant to carbapenems.A few pan-re-sistant strains of K.pneumoniae (0.7%,4/615)were iden-tified.About 20.3% and 13.6% of the P .aeruginosa isolates were resistant to imipenem and meropenem,respectively.P . aeruginosa isolates showed the lowest resistance rate (7.2%)to amikacin.And 72.8% and 75.2% of A.baumannii strains were resistant to imipenem and meropenem.A.baumannii isolates showed relatively low resistance rate to cefoperazone-sulbac-tam (51.2%)and minocycline (30.2%).The prevalence of pan-resistant strains was 43.5% in A.baumannii and 1.4% in P . aeruginosa.Conclusions Bacterial resistance is still increasing,especially pan-resistant A.baumannii strains.It is mandatory to take effective measures to control hospital infections and improve rational antibiotic use.

Object To establish a calli culture system for the rapid propagation of Speiraea japonica L. f.. Methods Callus and shoot induction were carried out on MS, 6, 7 V or B 5 media with different parts of the plant such as stem tip, tender leaves and petiole as explants. Results A calli culture system was established for the rapid propagation of S. japonica. Conclusion MS cultural medium was found to be most suitable for calli induction. MS with 2.0 mg/L 2,4 D+0.3 mg/L KT can induce calli when the explants were used for the induction, with stem tips being the most satisfactory explant. Clusters of seedlings can be induced on MS+2 mg/L BA+0.1 mg/L NAA and when these seedlings were transferred to 1/2 MS +0.25 mg/L BA+0.5 mg/L NAA medium, root were developed to give young seedlings.